As KORs inhibit both glutamate release onto NAcc medium-sized spiny neurons (MSNs) via a presynaptic site of action, we first determined whether KORs differentially regulated glutamatergic inputs to the NAcc.. Moreover, we find that KORs inhibit basolateral amygdala (BLA), but not ventral hippocampal afferents to MSNs. KORs are directly situated on BLA terminals to NAcc as genetic ablation of BLA KORs blocks prevents KOR agonist inhibition of glutamate release from BLA terminals and increases the basal probability of glutamate release. We next determined whether KORs were differentially inihibiting glutamate and GABA release onto the two projection neurons of the NAcc, D1 and D2 MSNs, which play opposing roles in reward and mood. KORs inhibit glutamatergic afferents to D1 MSNs an effect that is not evident in D2 MSNs. KORs also inhibit glutamate release from BLA afferents onto D1 MSNs but not D2 MSNs. Intriguingly, KORs inhibit GABA release onto both D1 and D2 MSNs. Furthermore, D1 MSN GABAergic inputs to other MSNs are also inhibited by KORs. Thus, KOR signaling changes excitation and inhibition to differentially change in D1 and D2 MSNs. We are also actively investigating how endogenous dynorphin release may impact synaptic transmission in the NAcc. Strong, but not weak, optogenetic activation of populations D1 MSNs, which express dynorphin, causes the release of dynorphin to act on KORs glutamatergic afferents. As dynorphin-mediated inhibition of glutamate release is present in cells activated and not activated by optogenetic stimulation and strong activation of a single D1 MSN with similar stimulation patterns is not sufficient to inhibit presynaptic glutamate release, KOR-mediated inhibition of glutamate release may not be a consequence of dynorphin release from the recorded neuron. Interestingly the same optogenetic stimulation pattern that causes dynorphin release onto glutamatergic synapses does not modify GABAergic transmission evoked electrically or optogenetically from D1 MSNs to other MSNs. Taken together, these results suggest that released endogenous dynorphins inhibit glutamatergic transmission via volume transmission, but are restricted with regards to GABAergic synapses. Collectively, here we show that the endogenous dynorphin/kappa-opioid receptor system modulates information processing in the NAcc by differentially regulating glutamatergic and GABAergic synapses onto D1 and D2 MSNs. Moreover, we also provide the first demonstration that D1 MSNs utilize endogenous opioid systems to influence synaptic transmission onto other